设计并合成新型咪唑并[4,5-b]吡啶类化合物作为具有 CDK9 抑制活性的强效抗癌剂。
Design and synthesis of novel imidazo[4,5-b]pyridine based compounds as potent anticancer agents with CDK9 inhibitory activity.
机构信息
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
出版信息
Bioorg Chem. 2018 Oct;80:565-576. doi: 10.1016/j.bioorg.2018.07.006. Epub 2018 Jul 6.
New imidazo[4,5-b]pyridine derivatives were designed, synthesized and screened for their anticancer activity against breast (MCF-7) and colon (HCT116) cancer cell lines. Nine compounds (I, II, IIIa, IIIb, IV, VI, VIIa, VIII, IX) showed significant activity against MCF-7, while six compounds (I, VIIc, VIIe, VIIf, VIII, IX) elicited a remarkable activity against HCT116. Compounds showing significant anticancer activity revealed remarkable CDK9 inhibitory potential (IC = 0.63-1.32 μM) relative to sorafenib (IC = 0.76 μM). Moreover, a molecular docking study was performed to illustrate the binding mode of the most active compounds in the active site of CDK9 where it revealed superior binding affinity relative to the natural ligand (T3C).
新型咪唑并[4,5-b]吡啶衍生物被设计、合成并筛选其对乳腺癌（MCF-7）和结肠癌（HCT116）癌细胞系的抗癌活性。九种化合物（I、II、IIIa、IIIb、IV、VI、VIIa、VIII、IX）对 MCF-7 表现出显著的活性，而六种化合物（I、VIIc、VIIe、VIIf、VIII、IX）对 HCT116 表现出显著的活性。表现出显著抗癌活性的化合物显示出显著的 CDK9 抑制潜力（IC = 0.63-1.32 μM），相对于索拉非尼（IC = 0.76 μM）。此外，还进行了分子对接研究，以说明最活性化合物在 CDK9 的活性部位的结合模式，其显示出相对于天然配体（T3C）的优越结合亲和力。
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